Is F10 p.Arg346Cys (c.1036C>T) pathogenic?

F10 p.Arg346Cys (c.1036C>T) is classified Likely pathogenic in F10 (ClinVar, Single submitter, 1 submitter). AlphaMissense: ambiguous (0.5452); Very rare (popmax 0.00223%, eas); Associated with congenital factor X deficiency.

What condition is associated with F10 p.Arg346Cys (c.1036C>T)?

F10 p.Arg346Cys (c.1036C>T) is associated with congenital factor X deficiency (ClinVar).

How common is F10 p.Arg346Cys (c.1036C>T) in the general population?

F10 p.Arg346Cys (c.1036C>T) is very rare (popmax 0.00223%, eas) (gnomAD).

How is Congenital factor X deficiency inherited?

Typically Autosomal recessive (Orphanet). A genetic counselor can assess individual risk for a family.

What do computational predictors say about F10 p.Arg346Cys (c.1036C>T)?

AlphaMissense predicts ambiguous (score 0.5452) — an in-silico prediction, not a clinical call.

F10 p.Arg346Cys

c.1036C>T · rs755110383 · VCV2572129

Likely pathogenic Single submitter

Classification

Likely pathogenic

ClinVar

Review

Single submitter ★☆☆☆

ClinVar · 1 submitter

AlphaMissense

ambiguous

0.5452 · ACMG-weighted

gnomAD v4.1

Rare

very rare (popmax 0.00223%, eas)

Conditions

congenital factor X deficiency

Computational evidence

Protein change
AlphaMissense	0.5452	ambiguous
REVEL	0.479	indeterminate
SaProt	LLR -10.11	damaging
Splicing
SpliceAI	—	not assessed · no allele here is in the release
Constraint at this position
Conservation	phyloP 5.8	GERP 0.75, phastCons 1
Regional constraint	o/e 0.75	unconstrained · MANE · 10 kb · p 2.9e-09 · regional, not allelic
Overall
CADD	22.8	PHRED · no single calibrated threshold — expert panels disagree

AlphaMissense carries the ACMG weight for missense; REVEL and SaProt are independent agreement signals.

Population frequency

gnomAD v4.1 · exomes + genomes

Grpmax group 0.00223% East Asian · 1/44,892 alleles

Filtering AF 2.8e-05% ClinGen BA1/BS1 input FAF95, joint · FAF99 1.1e-05%

Overall 0.000248% 4/1,613,122 alleles · very rare

Ancestry group	Frequency	1 in
East Asiangrpmax	0.00223%	44,892
South Asian	0.0011%	91,078
European (non-Finnish)	0.000169%	590,002

Rarity supports pathogenicity (ACMG PM2); frequency above a disease-specific BA1/BS1 threshold argues against it. A variant frequent in one ancestry group can be near-absent in others, so a single global figure can mislead.

Variant & gene context

Gene: F10
Protein: p.Arg346Cys
Coding: c.1036C>T
MANE Select: NM_000504
dbSNP: rs755110383
Type: single nucleotide variant
Location: chr13:113149086 (GRCh38)
Gene constraint: LOEUF 0.968 · pLI <0.01 (gnomAD)
Structure: AlphaFold pLDDT 80.47 · 192 PDB
Residue 346: the peptidase s1 domain

Full F10 gene report on Sugi Atlas → Gene function, pathways, protein structure, interactions & more

Disease context

congenital factor X deficiency — disease report on Sugi Atlas → Associated genes, phenotypes, clinical trials & treatments

For Congenital factor X deficiency (Orphanet):

Inheritance: Autosomal recessive
Onset: All ages
Prevalence: 1-9 / 1 000 000 (Europe)

Similar variants

F10 p.Glu54Gly Likely pathogenic ★★ same condition
F10 p.Gly363Ser Likely pathogenic ★★ same condition
F10 p.Gly450Arg Likely pathogenic ★★ same condition
F10 p.Arg291Gln Uncertain significance ★★ ⚠ same condition
F10 p.Glu306Lys Uncertain significance ★★ ⚠ same condition
F10 p.Gly106= Uncertain significance ★★ same condition
F10 p.Gly154Arg Uncertain significance ★★ ⚠ same condition
F10 p.Pro472Leu Uncertain significance ★★ ⚠ same condition

Built on 18 open, versioned datasets — ClinVar, gnomAD, AlphaMissense, REVEL, ClinGen & more — plus Sugi Variant's own cross-source analysis. Source data 2026-01–2026-10, ClinVar 2026-10. Full sources & versions →

Cite Sugi Variant

Gür T. Sugi Variant: A Deterministic Per-Variant Germline Reference from a Knowledge Graph for Humans and AI Agents. 2026. doi:10.5281/zenodo.21509445. This variant: https://sugi.bio/variant/f10-p-arg346cys (accessed [today's date]).

Preprint & method: sugi.bio/variant/method Machine-readable: this page as Markdown